Down's syndrome (DS) is a neurodevelopmental genetic disorder affecting millions of Americans. Periodontitis is a major oral health problem among these patients. Several studies showed an association between altered neutrophil (PMN) function, presence of periodontopathic bacteria and periodontitis among DS patients. While recent evidence shows that interleukin-1 (IL-1) is an important mediator of periodontal tissue destruction, the role of IL-1 in periodontitis associated with DS patients has never been investigated. This application will focus on several determinants of IL-1 levels and their role in the development of periodontitis among DS patients. Our central hypothesis is that IL-I overproduction initiates an extensive gingival inflammatory response leading to destruction of soft and hard tissues and the development of periodontitis in DS patients. Specifically we will examine IL-1 gingival crevicular fluid (GCF) levels and periodontitis in DS patients and non-DS controls and will evaluate mechanisms that have the potential to explain the levels of IL-1, including: a) the carriage of certain single-nucleotide polymorphisms of IL-1 genes, b) the carriage of specific bacterial species, and c) the dysfunction of PMNs. A total of 100 DS patients will be recruited, 50 with and 50 without periodontitis. Two comparison groups will also be recruited, with a similar number of periodontitis patients and controls. The first will be sampled from among non-Down's individuals with developmental or motor disorders living in the same group homes as the DS patients, and the second will be recruited from a dental clinic. Procedures to be used: (1) oral care behavior interview to determine accessibility to dental/oral care. (2) plaque index to determine level of oral hygiene. (3) gingival index and bleeding on probing to determine gingival inflammation. (4) probing measurements to determine periodontal attachment levels. (5) GCF sample collection to determine IL-1 levels. (6) Subgingival microbiological sample to determine presence of periodontopathic bacteria. (7) blood sample for genotyping and PMN function tests. Data will be used to produce a model for the severity of periodontitis for the Down's group as a function of the genotype, PMN function, bacterial load, hygiene, IL-1 levels, and demographic risk factors for periodontitis. This model of the mechanisms accounting for the severity of periodontitis will be compared to that found in the non-Down's sample.